Maternal toxicity, embryolethality and abnormal fetal development in CD‐1 mice following one oral dose of T‐2 toxin

Rousseaux, Colin G.; Schiefer, H. B.

doi:10.1002/jat.2550070410

Cited by 37 publications

(17 citation statements)

References 31 publications

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“…From the present study, we could not prove to what extent the placental dysfunction affects the fetal abnormalities and fetal growth retardation. It is known that some toxicants such as ENU [17], Ara-C [27], busulfan [10], T-2 toxin [22], azacytidine [15], adrenomedullin antagonist [26] etc., induce small placenta and fetal growth restriction in rats or mice, although their induced fetal abnormalities are different from the ones in 6-MP. Therefore, 6-MP-induced fetal abnormalities seem to be caused by its specific direct anti-proliferative effects during organogenesis.…”

Section: Discussionmentioning

confidence: 99%

Effect of 6-Mercaptopurine on Rat Placenta

et al. 2008

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ABSTRACT. In order to investigate the toxic effects of 6-mercaptopurine (6-MP) on placental development, we examined sequential morphology in the placentas from rats exposed to 6-MP. 6-MP was intraperitoneally administered at 60 mg/kg during gestation days (GDs) 11 to 12, and the placentas were sampled on GD 13, 15 or 21. In the 6-MP-treated group, maternal body weight suppression, increased death embryo/fetus ratio and some malformations were observed. The placenta weights were decreased on GDs 15 and 21. Macroscopically, placentas on GD 21 were small, brittle and thin with a white peripheral rim. Histopathologically, in the labyrinth zone, 6-MP treatment mainly evoked decreased mitosis on GDs 13 and 15, increased apoptotic cell on GDs 13, 15 and 21 and thinning on GDs 15 and 21. In the basal zone, 6-MP evoked decreased mitosis on GDs 13, and PAS-positive material in the spongiotrophoblasts was still detected on GD 15. Thickening of the basal zone was observed with cytolysis of glycogen cells, apoptosis and an increased number of composed cells on GD 21. In conclusion, 6-MP administration in pregnant rats induced growth arrest of the labyrinth zone and developmental delay in the basal zone, leading to small placentas. The fetotoxicity of 6-MP may be responsible for its direct anti-proliferative effects and resulting placental dysfunction.

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Section: Discussionmentioning

confidence: 99%

Effect of 6-Mercaptopurine on Rat Placenta

et al. 2008

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“…Apoptosis in the central nervous system and cartilage primordium was observed in the fetuses from dams treated with T-2 toxin 11,12,25 . In the present study on rats, single cell necrosis was observed in the nervous system and liver of fetuses.…”

Section: Discussionmentioning

confidence: 99%

“…It is known that T-2 toxin has cytotoxic effects due to its inhibitory effects on protein synthesis and DNA synthesis, and these effects may produce necrosis/ apoptosis 9,10 . It is said that pregnant mice treated with T-2 toxin exhibited fetal death and fetotoxicity mainly in the central nervous and skeletal systems in addition to maternal toxicity [11][12][13] . In rats, it is reported that T-2 toxin passes the placenta and distributes to fetal tissues, resulting in an impairment of the immune system 14 .…”

Section: Introductionmentioning

confidence: 99%

T-2 Toxin-Induced Morphological Changes in Pregnant Rats

et al. 2003

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Pregnant Wistar rats on day 13 of gestation were treated with T-2 toxin at a single oral dose of 2 mg/kg. Rats were sacrificed at 24 and 48 hours after treatment (HAT), and the dams, placenta and fetuses were subjected to histopathological examination. In the dams treated with T-2 toxin, single cell necrosis was observed in the thymus, spleen, liver, stomach, intestines, salivary glands and pancreas. In the liver, fatty change was also observed. In one dam at 24 HAT, hemorrhage from the vagina was observed macroscopically, and hemorrhage in the placenta and single cell necrosis of cytotrophoblasts were observed microscopically. In the fetuses, increase of single cell necrosis was observed in the central nervous system at 24 HAT. At 48 HAT, single cell necrosis of hematopoietic cells and hepatocytes was also increased in the liver. These results indicate that T-2 toxin may induce changes with similar histopathological nature in dam's organs, placentae and fetuses. These results also suggest that changes observed in the fetuses are caused by the direct effect of T-2 toxin. (J Toxicol Pathol 2003; 16: 59-65)

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“…T-2 toxin readily crosses the placenta, is distributed to the fetal tissues 94 and induces fetal death, necrosis of the fetal brain and fetal bone malformations 95 . In addition, thymic atrophy and decreases in the viability of hematopoietic progenitor cells in the liver and in the number of B cells have also been reported in fetuses from dams exposed to T-2 toxin 41,43 .…”

Section: Fetal Tissuesmentioning

confidence: 99%

“…Moreover, changes attributable to T-2 toxin-treatment have been reported in the nervous system, liver, gastrointestinal tract and cartilage primordium in rat fetuses 96,97 . Bone malfomations such as incomplete ossification, absence of bones, wavy bones and fused bones 95,[98][99][100] may be related to the induction of apoptosis in the caudal half of the sclerotome around the notochord, and in the mesenchyme, chondroblasts and chondrocytes around the cartilage primordium detected in fetuses from dams treated with T-2 toxin 101 . Ishigami et al 102 first reported that T-2 toxin could induce apoptosis especially in the central nervous and skeletal systems after oral administration of T-2 toxin to pregnant mice (Fig.…”

Section: Fetal Tissuesmentioning

confidence: 99%

T-2 Toxin and Apoptosis

2006

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T-2 toxin is a cytotoxic fungal secondary metabolite produced by various species of Fusarium. This paper reviews the reported data about the development and/or mechanisms of T-2 toxin-induced apoptosis in the hematopoietic, lymphoid and gastrointestinal tissues, dorsal skin and fetal tissues of mice and rats. Apoptosis occurs earlier in hematopoietic tissues than in lymphoid tissues, and moreover there is a difference among lymphocyte populations in the susceptibility to T-2 toxin. C-fos plays an important role in the early phase of T-2 toxin-induced apoptosis in hematopoietic and lymphoid tissues through mobilization of [Ca 2+ ] i and the PKC-dependent pathway, but not through Fas/Fasligand or p53-related pathways. In the gastrointestinal tract, apoptosis develops earlier in the small intestine than in the stomach, and is more prominent in the small intestine than in the large intestine. In the dorsal skin topically treated with T-2 toxin, epidermal basal cell proliferating activity is first suppressed due to the elevated TGF-β 1 expression, and then basal cell apoptosis develops concomitantly with the elevation of c-fos, c-jun and TNF-α mRNAs expression. In the fetuses, T-2 toxin-induced apoptosis is mainly observed in the central nervous and skeletal systems. In the fetal brain, T-2 toxin induces oxidative stress, followed by activation of the MAPK-JNK-c-Jun pathway, finally resulting in apoptosis. The TNF receptor pathway may also be involved in T-2 toxin-induced apoptosis in the fetal brain. Thus, the development and mechanisms of T-2 toxin-induced apoptosis differ somewhat depending on the tissues affected. (J Toxicol Pathol 2006; 19: 15-27)

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Maternal toxicity, embryolethality and abnormal fetal development in CD‐1 mice following one oral dose of T‐2 toxin

Cited by 37 publications

References 31 publications

Effect of 6-Mercaptopurine on Rat Placenta

Effect of 6-Mercaptopurine on Rat Placenta

T-2 Toxin-Induced Morphological Changes in Pregnant Rats

T-2 Toxin and Apoptosis

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